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Clin Infect Dis. 2019 Mar 16. pii: ciz212. doi: 10.1093/cid/ciz212. [Epub ahead of print]

Circulating (1→3)-β-D-Glucan is associated with immune activation during HIV infection.

Author information

1
Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC, Canada.
2
Infectious Diseases and Immunity in Global Health Program, Research Institute, McGill University Health Centre, Montreal, QC, Canada.
3
Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.
4
Department of Microbiology and Immunology, McGill University, Montreal, QC, Canada.
5
Department of Laboratory Medicine, University Medical Center, University of Groningen, the Netherlands.
6
Department of Biological Sciences, University of Quebec at Montreal (UQAM), Montreal, QC, Canada.
7
Department of Family Medicine, McGill University, Montreal, QC, Canada.
8
Clinique Médicale l'Actuel, Montréal, QC, Canada.
9
Clinique Médicale Quartier Latin, Montréal, QC, Canada.
10
Clinique Médicale Opus, Montréal, QC, Canada.
11
Département de microbiologie, infectiologie et immunologie, Faculté de médecine, Université de Montréal, Montréal, QC, Canada.
12
Division of Hematology, McGill University Health Centre, Montreal, QC, Canada.

Abstract

BACKGROUND:

Microbial translocation from the gut to circulation contributes to immune activation during HIV infection and is usually assessed by measuring plasma levels of bacterial lipopolysaccharide (LPS). Gut fungal colonization increases during HIV infection and elevated systemic levels of the fungal polysaccharide (13)--D-Glucan (DG) have been reported in people living with HIV (PLWH). We assessed plasma DG in 146 early and chronic PLWH and investigated its contribution to systemic immune activation.

METHODS:

Cross-sectional and longitudinal assessment of plasma DG levels were conducted along with markers of HIV disease progression, epithelial gut damage, bacterial translocation, pro-inflammatory cytokines, and DG-specific receptor expression on monocytes and NK cells.

RESULTS:

Plasma DG levels were elevated during early and chronic HIV infection and persisted despite long-term ART. DG increased over 24-months without ART (p=0.01) but remained unchanged after 24-months of treatment (p>0.99). DG correlated negatively with CD4 T-cell count (r=-0.252; p<0.001), and positively with time to ART initiation (r=0.254; p=0.04), viral load (r=0.350; p=0.002), I-FABP (r=0.384; p=0.001), LPS (r=0.267; p<0.001), and sCD14 (r=0.388; p=0.001). Elevated DG correlated positively with IDO-1 enzyme activity (r=0.345; p=0.004), Tregs frequency (r=0.410; p=0.006), activated CD38+HLA-DR+ CD4 (r=0.652; p<0.001) and CD8 T-cells (r=0.687; p<0.001), and negatively with Dectin-1 (r=-0.474; p=0.01) and NKp30 (r=-0.614; p=0.009) expression on monocytes and NK cells, respectively.

CONCLUSION:

PLWH have elevated plasma DG in correlation with markers of disease progression, gut damage, bacterial translocation and inflammation. Early ART initiation prevents further DG increase. This fungal antigen contributes to immune activation and represents a potential therapeutic target to prevent non-AIDS events.

KEYWORDS:

(1→3)-β-D-Glucan; Anti-retroviral therapy; HIV; Immune activation; LPS; Microbial translocation

PMID:
30877304
DOI:
10.1093/cid/ciz212

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